Lack of effect of thyroxine in patients with Graves' hyperthyroidism who are treated with an antithyroid drug

N Engl J Med. 1996 Jan 25;334(4):220-4. doi: 10.1056/NEJM199601253340403.


Background: Antithyroid drugs are effective in patients with hyperthyroidism due to Graves' disease, but the rate of recurrence after treatment is high. In a recent Japanese study, adjunctive treatment with thyroxine (T4) was associated with a recurrence rate 20 times lower than that among patients who received only an antithyroid drug. If these results are confirmed, combined therapy with an antithyroid drug and T4 might become the treatment of choice for all patients with Graves' hyperthyroidism.

Methods: We treated 111 patients (89 women and 22 men) who had Graves' hyperthyroidism. All patients initially received 40 mg of carbimazole daily for one month. Then one group received carbimazole alone for 17 months (52 patients), and the other group received carbimazole plus T4 for 17 months and T4 alone for 18 months (59 patients). In the carbimazole group, the dose was adjusted after one month to maintain a normal serum thyrotropin concentration. In the carbimazole-T4 group, the dose of carbimazole was not changed, but 100 micrograms of T4 per day was added to the regimen and the dose was adjusted to maintain an undetectable serum thyrotropin concentration (< 0.04 microU per milliliter).

Results: At the time of our analysis, 53 of the 111 patients had completed at least 3 months of follow-up (median, 12 months) after carbimazole was withdrawn. Hyperthyroidism recurred in eight patients in each group after a mean (+/- SD) of 6 +/- 4 months in the carbimazole group and 7 +/- 4 months in the carbimazole-T4 group. There was no difference between the recurrence rates in the two groups, despite the fact that serum thyrotropin concentrations were undetectable in 73 percent of patients in the carbimazole-T4 group on at least 75 percent of their visits.

Conclusions: The administration of T4 to patients with Graves' disease during carbimazole treatment and after its withdrawal neither delays nor prevents the recurrence of hyperthyroidism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies / blood
  • Antithyroid Agents / therapeutic use*
  • Carbimazole / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Graves Disease / drug therapy*
  • Humans
  • Male
  • Receptors, Thyroid Hormone / immunology
  • Recurrence
  • Thyroxine / blood
  • Thyroxine / therapeutic use*
  • Treatment Outcome
  • Triiodothyronine / blood


  • Antibodies
  • Antithyroid Agents
  • Receptors, Thyroid Hormone
  • Triiodothyronine
  • Carbimazole
  • Thyroxine